How does fluoroaluminate activate human platelets?
Platelet activation induced by NaF or fluoroaluminate (AlF4-) was studied. The latter has been described to substitute for the gamma-phosphate group of the GTP molecule. With 10 mM-NaF, a concentration unable to induce any measurable Ca2+ mobilization (as measured with Indo 1), addition of AlCl3 potentiated platelet aggregation, thromboxane synthesis, diacylglycerol formation and p43 phosphorylation, without any increase in intracellular Ca2+. Neither phosphoinositide hydrolysis nor phosphatidic acid formation could be detected. AlF4- induced the release through a granule centralization within a microtubule bundle, although no myosin light-chain phosphorylation could be detected. Addition of flurbiprofen (10 microM) resulted in only partial inhibition of diacylglycerol formation, with no effect on the release reaction or on p43 phosphorylation. The present results suggest that AlF4- does not stimulate a G-protein governing the phosphoinositide-specific phospholipase C. The AlF4(-)-induced diacylglycerol formation is discussed. Moreover, these results bring evidence that there is no correlation between granule centralization and myosin light-chain phosphorylation.
Rendu
F
F
U 150 INSERM, URA 334 CNRS, Hôpital Lariboisiere, Paris, France.
Lebret
M
M
Tenza
D
D
Levy-Toledano
S
S
D000535:Aluminum / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D002118:Calcium / Q000097:blood; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000648:ultrastructure; D004075:Diglycerides / Q000097:blood; D005461:Fluorine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D015879:Myosin Subfragments / Q000097:blood; D010766:Phosphorylation; D015539:Platelet Activation; D010974:Platelet Aggregation; D012701:Serotonin / Q000097:blood; D012969:Sodium Fluoride / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
D004075:Diglycerides; D015879:Myosin Subfragments; C053629:fluoroaluminum; D005461:Fluorine; D012701:Serotonin; D013929:Thromboxane B2; D012969:Sodium Fluoride; D000535:Aluminum; D002118:Calcium